The use of the rat in developmental immunotoxicology studies.

The benefits and costs are discussed for the possibility of using pups generated in breeding studies for additional assessments, such as evaluating immunotoxicity. Such an approach is logistically challenging, but not overwhelming.

Aging in place in assisted living: philosophy versus policy.

PURPOSE: Support of older adults' capacity to age in place is a core concept of the assisted living philosophy. This research examined implementation of the aging-in-place philosophy in 1 midwestern state (Kansas). DESIGN AND METHODS: This study was part of a larger state agency and university collaborative project to examine admission and discharge policies in these settings. Data analysis was conducted with descriptive statistics. Kansas findings were compared to national findings. RESULTS: Residents' capacity to age in place was limited by facility admission and discharge policies that were more restrictive than state regulations in the areas of behavioral problems, incontinence, and cognition. In general, assisted living facility policies in Kansas were more restrictive than admission and discharge policies found nationally. IMPLICATIONS: More inclusive assisted living admission and discharge criteria, and concomitant staffing and funding, are necessary if the aging-in-place philosophy is to be more fully implemented.

The legislative tenets of client's right to treatment in the least restrictive environment and freedom from harm: implications for community providers.

For over four decades, national legislation has supported efforts to move persons with severe and persistent mental illness out of restrictive hospital settings and into community based services. Within institutional walls, numerous duties of state have been established to help ensure humane and effective treatment. However, the legal protections afforded hospitalized residents have not appeared to follow these individuals into the community. This article analyzes relevant case law and attempts to establish similarities between the state hospital's duty to protect its residents and the responsibility of community mental health centers to do the same for the persons they serve. The authors argue that the client's right to freedom-from-harm must receive increased attention and community based service providers will have to enhance their capacity to deliver more effective risk management services if mental health reform is to become a successful social policy.

Expedited service delivery: helping case managers to increase access to services for the poorest older adults.

Low-income older adults have historically received institutionally based care when they were unable to care for themselves and there was a lack of sufficient formal and informal support to allow them to remain in their own homes. In 1981, revision of federal Medicaid legislation permitted states to provide home- and community-based services (HCBS) for older adults at risk of nursing facility placement in an attempt to prevent unnecessary placement and to offer choice. However, Medicaid-HCBS applicants may have to wait up to 45 days or longer for approval of their financial application. During those 45 days, the applicant may enter a nursing facility because Medicaid-HCBS was not available soon enough to prevent placement. This article presents research on an instrument to help case managers initiate community-based in-home services for the lowest-income Medicaid applicants within 3 to 5 days of initial assessment.

Going home: community reentry of light care nursing facility residents age 65 and over.

Issues of consumer choice, and rising public expenditures of nursing facility care for the rapidly increasing elderly population have fueled interest in community reentry of nursing facility residents. The Minimum Data Set Plus (MDS+) contains a wealth of information which can be used to provide a better understanding of nursing facility residents including those who discharge. This study employs the Andersen model of health services utilization and logistical regression on MDS+ data to examine characteristics of higher functioning nursing facility residents age 65 and over related to community reentry in one midwestern state. Findings include having Medicaid as a payer source significantly decreased the likelihood of discharge. In contrast, being younger than 85, retaining decision making responsibilities, and having no cognitive impairments were found to increase the likelihood of discharge. Policy and program implications related to identifying and assisting nursing facility residents in resuming community living are discussed.

The relationships among reproductive endpoints in Swiss mice, using the reproductive assessment by Continuous Breeding database.

The database of Continuous Breeding mouse studies was evaluated to determine the relationships between the functional indicators of reproduction (pup measures) and the various necropsy endpoints collected for males and females. Of 72 chemicals studied, both males and females were affected in 33 studies, while females and/or conceptuses were affected in 7. Two compounds affected only males, 17 studies were negative, and in 13 studies with effects it was not possible to clearly determine the affected gender(s). Greater F0 dam weight was correlated with increased pup mass per litter; this relationship was strongest for the first litter, and weakest for the fifth litter. For both generations of treated females (F0 and F1), longer estrous cycles correlated with reduced numbers of pups; the relationship was stronger in F0 than in F1 females and was not seen in controls. Sperm parameters had different distributions in treated mice than in control mice. Fertility (total live pups/number of pairs cohabited) was reduced if there were > approximately 15% sperm abnormalities or if sperm motility (moving/not moving) was < approximately 37%. Both of these relationships appeared to have thresholds. Epididymal sperm count in treated animals, however, was linearly related to fertility, even within the control range, suggesting strongly that other factors are important. Using both treated and control data together, combining sperm count with motility could explain much (r = 0.77) of the variation in fertility; adding morphology did not significantly improve the correlation. The model was almost as strong using count and morphology, in which case adding motility did not strengthen the model. This analysis of these studies shows that while some endpoints (e.g., random-estrous-cycle-point ovary weight) correlate poorly with fertility, other necropsy endpoints (epididymal sperm count and motility, estrous cycle length, and testis and epididymal weights) can be useful (though not complete) surrogates of overall reproductive function. Indeed, over many studies, epididymal sperm count in treated animals correlates with fertility so well that even small reductions (approximately 20%) in count result in reduced fertility, suggesting that mice may be better models of human fertility than was previously believed.

Reproductive assessment by continuous breeding: evolving study design and summaries of ninety studies.

The Reproductive Assessment by Continuous Breeding (RACB) design has been used by the National Toxicology Program for approximately 15 years. This article details the evolutions in the thinking behind the design and the end points used in the identification of hazards to reproduction. Means of nominating chemicals are provided, and both early and current designs are described as well as some proposed changes for the future. This introduction is followed by a text and tabular summary of each study performed to date. We hope that this will not only be an explicit presentation of the findings of this testing program to date, but will help stimulate thinking about new ways to detect and measure reproductive toxicity in rodents, and help identify new relationships among the end points that are measured in such studies.

The strengths model in long-term care: linking cost containment and consumer empowerment.

This article outlines how the strengths model of case management can be applied to long-term-care case management. The strengths model was first articulated in the early 1980s as an alternative to brokered case management in mental health. The strengths approach to social service practice focuses on helping people and communities discover and develop their own capacities, talents, skills, and interests, and on connecting them with the resources needed to achieve their goals. This article explicates the components of the strengths model as adapted to long-term care. The authors explore the link between the application of strengths-based strategies at critical intervention points and cost containment, giving examples of how case managers serving older adults through Medicaid waivers have implemented the strengths approach and delayed nursing facility admissions. Finally, the authors describe ways that cost-containment methods can be interfaced with a consumer-driven empowerment orientation. Initial responses gathered from consumers and long-term-care case managers trained in the strengths model support its applicability to older adults. Clear articulation of how the strengths model of case management can be adapted for use with adults in need of long-term care is basic to further implementation and evaluation.

Assessment of the reproductive toxicity of a complex mixture of 25 groundwater contaminants in mice and rats.

The potential reproductive toxicity of a mixture of 25 chemicals (MIX) formulated to simulate contaminated groundwater supplies near hazardous waste dumps was evaluated in CD-1 Swiss mice and Sprague-Dawley rats using the reproductive assessment by continuous breeding protocol. Male and female mice and rats were exposed to MIX in the drinking water at concentrations of 1, 5, and 10% of a technically achievable stock solution. For mice, body weight and feed consumption were not affected by MIX but water consumption was decreased for both the 5 and 10% MIX groups in both F0 and F1 animals. For F0 mice, the number of live pups/litter was decreased at 10% MIX and the number of females/litter was decreased 10 and 17% at the mid and high MIX dose, respectively. Vaginal cytology was normal, as were testis weight and testicular spermatid head count. For F1 mice, fertility was unaffected, but there was a decreased number of female pups/litter (19%) and a decreased adjusted live pup weight at 10% MIX. At necropsy, cauda epididymal sperm concentration and spermatid head count were reduced (20%) in the presence of normal testis, epididymis, prostate, seminal vesicle, liver, and kidney/adrenal weight. Female estrous cyclicity was altered at 5 and 10% MIX with normal kidney/adrenal, uterus, and ovary/oviduct weight. For rats, F0 body weight and feed consumption were not affected by MIX but water consumption was decreased 10, 30, and 40% in the low-, medium-, and high-dose MIX groups, respectively, and 39% in the high-dose MIX F1 animals. Rat fertility was normal but there was a decreased number of male pups/litter (11%) and a decreased live pup weight (6%) at 10% MIX. Male and female (F1) pup weights were decreased on Postnatal Days 0, 4, 7, 14, and 21 (10% MIX) and remained lower through necropsy on Day 120 +/- 10. F1 fertility was normal but F2 pup weights were decreased (10% MIX). At necropsy, F1 (10% MIX) male body weight was decreased 16% and relative kidney, testis, epididymis, and prostate weights were increased in the presence of normal sperm concentration percentage motile sperm and percentage abnormal sperm. Estrous cyclicity was normal as were kidney/adrenal and ovary weight while female liver weight was reduced 14%. In summary, a "cocktail" of 25 chemicals commonly found in contaminated groundwater at or near hazardous waste sites was administered in drinking water at doses which resulted in severely decreased water consumption in both mice and rats.(ABSTRACT TRUNCATED AT 400 WORDS)

Home care for children dependent on medical technology: the family perspective.

Children who are dependent on medical technology present unique challenges to families and professionals who attempt to care for them at home. This longitudinal, exploratory study examines the placement threatening crises experienced over an eighteen-month period by four such families in Minnesota. The findings encourage development of a family support model of placement prevention for this population, as opposed to a crisis intervention model.

Assessment of the reproductive and developmental toxicity of pesticide/fertilizer mixtures based on confirmed pesticide contamination in California and Iowa groundwater.

Pesticides and fertilizers, as used in modern agriculture, contribute to the overall low-level contamination of groundwater sources. In order to determine the potential of pesticide and fertilizer mixtures to produce reproductive or developmental toxicity at concentrations up to 100 x the median level found in groundwater, we prepared and studied two mixtures of pesticides and a fertilizer (ammonium nitrate). One mixture containing aldicarb, atrazine, dibromochloropropane, 1,2-dichloropropane, ethylene dibromide, and simazine plus ammonium nitrate was considered to be a representative of groundwater contamination in California (CAL). The other, containing alachlor, atrazine, cyanazine, metolachlor, metribuzin, and ammonium nitrate, simulated groundwater contamination in Iowa (IOWA). Each mixture was administered in the drinking water of either Swiss CD-1 mice during a Reproductive Assessment by Continuous Breeding study or pregnant Sprague-Dawley rats (gd 6-20) at three dose levels (1x, 10x, and 100x) where 1x was the median concentration of each pesticide component as determined in the groundwater surveys in California or Iowa. Unlike conventional toxicology studies, the purpose of this study was to evaluate the health effects of realistic human concentrations. Thus, the testing concentrations are probably well below the maximally tolerated dose. Propylene glycol was used as the solubilizer for the pesticides in drinking water formulations in both studies. In the reproductive study, neither mixture caused any clinical signs of toxicity, changes in food or water consumption, or body weight in either F0 or F1 mice at doses up to 100x the median groundwater concentrations. There were no treatment-related effects on fertility or any measures of reproductive performance of either the F0 or the F1 generation mice exposed to either CAL or IOWA at up to 100x. Similarly, measures of spermatogenesis, epididymal sperm concentration, percentage motile sperm, percentage abnormal sperm, and testicular and epididymal histology were normal. In the developmental study, CAL- or IOWA-exposed females did not exhibit any significant treatment-related clinical signs of toxicity. No adverse effects of CAL or IOWA were observed for measures of embryo/fetal toxicity, including resorptions per litter, live litter size, or fetal body weight. CAL or IOWA did not cause an increased incidence of fetal malformations or variations. In summary, administration of these pesticide/fertilizer mixtures at levels up to 100-fold greater than the median concentrations in groundwater supplies in California or Iowa did not cause any detectable reproductive (mice), general, or developmental toxicity (rats).

Assessment of a short-term reproductive and developmental toxicity screen.

Short-term tests for reproductive and developmental toxicity are needed to provide preliminary data on the toxicity of chemicals about which little or no data exist. An ideal design would test all aspects of reproduction and identify the target process in a short time period. One potential design has been evaluated using four chemicals of varying reproductive/developmental toxicity. Swiss mice were mated for 3 days prior to chemical exposure to produce time-mated females for gestational exposure and to ascertain fertility of the untreated males. The group of time-mated females was treated during Gestation Days 8-14 and allowed to litter for observations through Postnatal Day (PND) 4. Endpoints observed included pup number and body weights on PND 0, 1, and 4 and number of uterine implantation sites on PND 4. A second group of females was dosed daily for 19 days. After 7 days, these females (n = 10/group) were cohabited with male mice who had been treated for 5 days prior to this second mating. Daily chemical dosing continued during the 5-day cohabitation. This second group of females was killed after 19 days of treatment and the number of live and dead fetuses and implantation sites was recorded. After 17 days of dosing, male mice were killed and the reproductive system evaluated by organ weights, total epididymal sperm counts and motility, and testicular histology. All four chemicals tested, boric acid, ethylene glycol, ethylene glycol monomethyl ether, and theophylline, were found to be toxic to development or reproduction when tested previously by conventional developmental toxicity or continuous breeding protocols. This short-term (21 day) design correctly identified three of these four chemicals as reproductive and developmental toxicants and distinguished the potent toxicants from the less effective compounds. This design can be used to prioritize chemicals for further study, or to delineate the relative toxicities of structurally related chemicals, and to identify the proper dose range for subsequent toxicity studies.

Incentive payments to nursing homes based on quality-of-care outcomes.

The federal Omnibus Budget Reconciliation Act of 1987 specifies that a state may establish a program to reward--through public recognition, incentive payments, or both--nursing facilities that provide the highest quality care to residents entitled to Medicaid. As state policymakers, providers, and advocates consider development of systems for rewarding quality in nursing homes, including incentive payments based on resident outcomes, theoretical and practical dilemmas must be addressed. The article examines the impetus for combining incentives with outcome measures and the conceptual dilemmas that outcome-based payments pose. Issues basic to successful implementation of incentive payments to nursing homes based on quality of care outcomes are also delineated.

Reimbursement of ICFs/MR program costs based on client resource use.

In this article we have described the impetus, research, and recommendations for a new reimbursement system based on client resource use for ICFs/MR in Minnesota. Research to develop a targeted reimbursement strategy has been completed and a proposal for basing program rates on client resource use developed. Residents (N = 913) in a stratified sample of 65 facilities were assessed and staff resource use determined. Results showed that although predictors in the area of personal interaction, integration, and independence, activities of daily living, special treatment/medical complexity, and behavior accounted for a significant amount of variation in resource use, the unaccounted for variation was sufficiently large to support recommending a system that will base program rates on individual client resource use and the historical costs of individual facilities. Key design issues were also discussed.

Reproductive toxicity assessment by continuous breeding in Sprague-Dawley rats: a comparison of two study designs.

The protocol for Reproductive Assessment by Continuous Breeding (RACB) studies was originally designed to use mice as the test species. However, rats are commonly used for reproductive toxicity research and could be used in the basic RACB design. One of the studies reported below evaluated a standard murine RACB design using rats, which rears the fifth litter to test second generation fertility. The second design tested the logistics and feasibility of rearing the second litter for second generation fertility testing. The standard fifth litter design (L5) was modified slightly for rats by increasing the time allowed for gestation and delivery. Compared to rats rearing their second litter (L2), rats in this L5 design had more litters per pair during continuous breeding and maintained this fertility better over time, as evidenced by producing more pups per litter during the crossover mating segment. Both L2 and L5 rats gave sufficient pups to conduct the second generation fertility evaluation. In addition, the L5 design was easier to conduct and produced pups from gametes exposed to chemical throughout spermatogenesis, making it the preferred design for using rats in Continuous Breeding studies.

Semen analysis and fertility assessment in rabbits: statistical power and design considerations for toxicology studies.

Semen analysis is commonly used in evaluating human response to reproductive toxicants. Serial semen samples can be collected from rabbits and fertility assessed by artificial insemination, hence this species is potentially well suited for male reproductive toxicity studies that might be extrapolated to humans. However, the size and cost of rabbits often restricts the number of animals used, reducing the sensitivity of such studies. Therefore, it was of interest to optimize study design for semen analysis and fertility assessment in rabbits. Semen samples were collected weekly from sexually mature New Zealand white rabbits and a range of parameters was analyzed (Semen--pH, volume, osmolality; Sperm--number and concentration, morphology, viability, percentage motility, motion characteristics; Seminal plasma--fructose, citric acid, carnitine and protein concentrations, acid phosphatase activity). Male fertility was assessed by inseminating female rabbits with the minimum number of motile sperm required for normal fertility, determined to be one million. The within- and between-buck variabilities were determined for all parameters and used to calculate the statistical power of different study designs. The variability of sperm number and concentration was decreased when measured in four ejaculates collected within a short period of time rather than in a single ejaculate; this was not true of other endpoints measured. In addition, use of preexposure observations further increased the statistical power for all of the parameters. These data can be used to determine the optimum design for studies of male reproductive toxicity using rabbits, with particular regard to cost and the number of animals used.